NIMG-15. 2-HYDROXYGLUTARATE MAGNETIC RESONANCE SPECTROSCOPY IN ADULT BRAINSTEM GLIOMA PATIENTS

OBJECTIVE The onco-metabolite, 2-Hydroxyglutarate (2HG), is non-invasive biomarker for detecting isocitrate dehydrogenase (IDH) mutant glioma by MR-Spectroscopy. Especially 2HG-MRS may be useful in patients with brainstem lesions, where surgical biopsy presents high risk of neurological injury. Here, we examined the utility of 2HG-MRS for diagnosis of IDH mutant adult brainstem glioma. METHODS We conducted 3 tesla -MRS (3T-MRS) in 8 radiographically identified brainstem tumor (7 male and 1 female, median age 39). Single-voxel was localized from the T2-FLAIR using a 2HG-tailored MRS protocol (Philips, Achieva, PRESS, TE 35 ms). All patients underwent tumor biopsy using an intraoperative navigation system (Brain LABTM) or stereotactic biopsy system (Komai’s CT-stereotactic frame) before initial treatment. IDH and H3K27M status were diagnosed by IHC and DNA sequence. RESULTS 3 cases were H3K27M and 4 cases were IDH mutant (R132H 1 case, R132S 2 cases, and R132G 1 case). 1 case were neither H3K27M nor IDH mutant. H3-K27 and IDH1 mutations were mutually exclusive. All tumor located at pons. There were no significant radiological difference between H3K27M and IDH mutant in conventional MRI sequence. Pearson's chi-square test demonstrated that 2HG concentrations >1.5 mM were 100% sensitive and 75% specific for IDH mutant glioma (p = 0.0285). The median overall survival survival were 127 month in IDH mutant glioma (n=4) and 22.5 months in IDH wild-type glioma (n=4), respectively. CONCLUSIONS 2HG in adult brainstem glioma was detected by conventional 3T-MRS successfully. A noninvasive 2HG-MRS may be useful diagnostic modality for evaluating molecular status and prognosis in brainstem glioma noninvasively.

A Risk Stratification Model Based on a Population Analysis for Predicting Cancer Specific Survival in Pediatric Brain Stem Glioma.

Introduction: The aim of this study was to construct and validate a nomogram and risk stratification model for predicting cancer-specific survival (CSS) of pediatric brainstem glioma patients. Methods: Cases of pediatric brainstem glioma patients (<12 years) from 1998 to 2016 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database and demographic, clinicopathologic characteristics, treatments, and survival outcomes were analyzed. The total cohort was randomly divided into training and validation sets, followed by univariate and multivariate Cox regression analyses. A nomogram was constructed and risk stratification analysis incorporated using the selected variables from the multivariate analysis. The accuracy of the model was assessed using C-index and calibration curves. Results: A total of 806 pediatric cases with histologically confirmed diagnosis of brainstem glioma were selected and analyzed. Multivariate analysis showed that age, race, tumor size, grade and radiotherapy (P<0.05) were independent prognostic indicators of pediatric gliomas. For prediction of CSS, the C-index of the nomogram was 0.75, which shows a good predictive probability. Conclusion: The nomogram developed in this study for predicting survival of pediatric patients with histologically confirmed stem gliomas is the first to incorporate risk stratification. Combining nomogram and risk stratification system is a convenient tool to aid clinicians in the identification of high-risk patients and to perform targeted adjuvant treatment.

Surgical considerations for maximal safe resection of exophytic brainstem glioma in the pediatric age group

Background: Brainstem glioma is the leading cause of morbidity and mortality among all central nervous system tumors, especially in childhood as it represents about 20% of all pediatric brain tumors. Therefore, this study aimed to present our experience in a tertiary center in a developing country with limited resources for the surgical management of exophytic brainstem gliomas. Methods: This retrospective study included pediatric patients with brainstem (midbrain, pontine, or medullary) focal or diffuse gliomas whether low or high grade that had dorsal, ventral, or lateral exophytic component who were presented to our hospitals from January 2019 to January 2021. The patients’ data were collected, such as age, sex, preoperative and postoperative clinical condition, radiological data, surgical approach, extent of tumor removal, histopathology, follow-up period, and adjuvant therapy. Results: A total of 23 patients were included in this study. The telovelar approach was used in 17 patients, the supracerebellar infratentorial approach in three patients, and the retrosigmoid, transcerebellar, and occipital transtentorial approach once for each patient. Twenty patients underwent near-total excision, and three underwent subtotal excision. Two-thirds of our cases (17 patients) were low-grade gliomas, with the remaining one-third comprising entirely of either anaplastic astrocytoma (five patients) or glioblastoma multiforme (one patient). The follow-up period of the patients extended from 3 months to 24 months. Conclusion: Exophytic brainstem glioma surgery can result in good outcomes with minimal complications when near-total excision is attempted through a properly chosen approach and adherence to some surgical techniques and considerations.

Prediction of H3K27M-mutant Brainstem Glioma by Amide Proton Transfer Weighted Imaging and Its Derived Radiomics

Purpose H3K27M-mutant associated brainstem glioma (BSG) carries a very poor prognosis. We aimed to predict H3K27M mutation status by amide proton transfer weighted (APTw) imaging and radiomic features. Methods Eighty-one BSG patients with APTw imaging at 3T MRI and known H3K27M status were retrospectively studied. APTw values (mean, median and max) and radiomic features within manually delineated 3D tumor masks were extracted. Comparison of APTw measures between H3K27M-mutant and wildtype groups was conducted by two-sample Student’s T/Mann-Whitney U test and receiver operating characteristic curve (ROC) analysis. H3K27M-mutant prediction using APTw-derived radiomics was conducted using a machine-learning algorithm in randomly selected train (n=64) and test (n=17) sets. Sensitivity analysis with additional random splits of train and test sets, 2D tumor masks and other classifiers were conducted. Finally, a prospective cohort including 29 BSG patients was acquired for validation of the radiomics algorithm. Results BSG patients with H3K27M-mutant were younger and had higher max APTw values than those with wildtype. APTw-derived radiomic measures reflecting tumor heterogeneity could predict H3K27M mutation status with an accuracy of 0.88, sensitivity of 0.92 and specificity of 0.80 in the test set. Sensitivity analysis confirmed the predictive ability (accuracy range: 0.71-0.94). In the independent prospective validation cohort, the algorithm reached an accuracy of 0.86, sensitivity of 0.88 and specificity of 0.85 for predicting H3K27M-mutation status. Conclusion BSG patients with H3K27M-mutant had higher max APTw values than those with wildtype. APTw-derived radiomics could accurately predict a H3K27M-mutant status in BSG patients.

The Survival Benefits of Surgical Resection and Adjuvant Therapy for Patients With Brainstem Glioma

PurposeThe role of surgical resection in the treatment of brainstem glioma (BSG) is poorly understood. For pediatric low-grade (LGBSG) group, several monocentric small-scale retrospective studies reported contradictory conclusions. And there was no clinical study focused on surgical resection for adult or pediatric high-grade (HG) patient groups. This study aims to illustrate whether surgical resection and adjuvant therapy provide survival benefits for patients with histologically confirmed BSG.Patients and MethodsThis retrospective cohort study included 529 patients with histologically confirmed BSG in Surveillance Epidemiology and End Results (SEER) database from 2006-2015. Patients were divided into four groups by age and World Health Organization (WHO) grade. Kaplan-Meier curves of CSS were plotted by different treatment options to compare the survival probability. Univariate and multivariable analyses were then conducted to determine the prognosis effects of surgical resection and adjuvant therapy on cancer specific survival (CSS). All analyses were done in four different groups separately.ResultsThe final sample included 529 patients. The entire study population was divided into groups of pediatric LG (n=236, 44.6%), pediatric HG (n=37, 7.0%), adult LG (n=204, 38.6%) and adult HG (n=52, 9.8%). 52.7% (n=144) of pediatric patients had pilocytic astrocytoma and 45.3% (n=116) of adult patients had ependymoma. Pediatric LGBSG group had the highest gross total resection (GTR) rate (61.4%) and 5-year CSS rate (88.6%). Kaplan-Meier curves of pediatric LGBSG group revealed that patients treated with GTR had significantly better survival probability (P=0.033). Multivariable analysis identified GTR as independently significant predictor for prolonged CSS in pediatric LGBSG group (HR0.29, 95%CI 0.11-0.78, P=0.015); Surgical resection showed no relation to CSS in other patient groups. Kaplan-Meier curves of adult HGBSG group showed that patients treated with both RT and CT in adult HGBSG group had the best survival probability (P=0.02). However, multivariable analysis showed the combination of radiotherapy (RT) and chemotherapy (CT) was not significantly related to better CSS in adult HGBSG group (HR0.35, 95%CI 0.11-1.09, P=0.070). Adjuvant therapy didn’t associate with better CSS in other patient groups.ConclusionPediatric LGBSG group had the highest GTR rate and the most favorable clinical outcome. GTR can provide significant survival benefits for pediatric LGBSG group.